5-56924555-T-C

Variant names:

• chr5-56924555-T-C
• rs702680
• NM_001297599.2:c.925-513A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297598.2(MIER3):​c.940-513A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,106 control chromosomes in the GnomAD database, including 20,978 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (20978 hom., cov: 32)
• Consequence: MIER3 NM_001297598.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 8 publications found

Genes affected

MIER3 (HGNC:26678): (MIER family member 3) Predicted to enable histone deacetylase binding activity and transcription corepressor activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SETD9 (HGNC:28508): (SET domain containing 9) Predicted to enable lysine N-methyltransferase activity. Predicted to be involved in regulation of signal transduction by p53 class mediator. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297598.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER3	NM_001297599.2	MANE Select	c.925-513A>G		intron	N/A	NP_001284528.1
	MIER3	NM_001297598.2		c.940-513A>G		intron	N/A	NP_001284527.1
	MIER3	NM_152622.5		c.922-513A>G		intron	N/A	NP_689835.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER3	ENST00000381199.8	TSL:1 MANE Select	c.925-513A>G		intron	N/A	ENSP00000370596.3
	MIER3	ENST00000381226.7	TSL:1	c.940-513A>G		intron	N/A	ENSP00000370624.3
	MIER3	ENST00000381213.7	TSL:1	c.922-513A>G		intron	N/A	ENSP00000370611.3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74913 AN: 151988 Hom.: 20980 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.493 AC: 74929 AN: 152106 Hom.: 20978 Cov.: 32 AF XY: 0.487 AC XY: 36171 AN XY: 74342

African (AFR) AF: 0.266 AC: 11061 AN: 41520

American (AMR) AF: 0.426 AC: 6496 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2276 AN: 3466

East Asian (EAS) AF: 0.110 AC: 572 AN: 5186

South Asian (SAS) AF: 0.425 AC: 2046 AN: 4818

European-Finnish (FIN) AF: 0.650 AC: 6854 AN: 10550

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43817 AN: 67990

Other (OTH) AF: 0.523 AC: 1102 AN: 2108

Alfa AF: 0.512 Hom.: 4481

Bravo AF: 0.465

Asia WGS AF: 0.293 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.4
DANN	Benign	0.67
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs702680; hg19: chr5-56220382;